chr13-95587541-G-C

Variant names:

• chr13-95587541-G-C
• rs1159736769
• NM_198968.4:c.2216C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198968.4(DZIP1):​c.2216C>G​(p.Ala739Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A739V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DZIP1 NM_198968.4 missense, splice_region
• Scores: Splicing: ADA: 0.0002663
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

DZIP1 (HGNC:20908): (DAZ interacting zinc finger protein 1) Predicted to enable metal ion binding activity. Involved in cilium assembly; germ cell development; and spermatogenesis. Located in cytosol; microtubule organizing center; and nucleoplasm. Colocalizes with centriole. Implicated in mitral valve prolapse and spermatogenic failure 47. [provided by Alliance of Genome Resources, Apr 2022]

DZIP1 Gene-Disease associations (from GenCC):

• spermatogenic failure 47

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0904443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198968.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP1	NM_198968.4	MANE Select	c.2216C>G	p.Ala739Gly	missense splice_region	Exon 20 of 23	NP_945319.1	Q86YF9-1
	DZIP1	NM_014934.5		c.2159C>G	p.Ala720Gly	missense splice_region	Exon 19 of 22	NP_055749.1	Q86YF9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP1	ENST00000376829.7	TSL:1 MANE Select	c.2216C>G	p.Ala739Gly	missense splice_region	Exon 20 of 23	ENSP00000366025.2	Q86YF9-1
	DZIP1	ENST00000361396.6	TSL:1	c.2159C>G	p.Ala720Gly	missense splice_region	Exon 19 of 22	ENSP00000355175.2	Q86YF9-2
	DZIP1	ENST00000926439.1		c.2270C>G	p.Ala757Gly	missense splice_region	Exon 17 of 20	ENSP00000596498.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461548 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111782

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.3
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.039
Sift	Benign	0.047	D
Sift4G	Uncertain	0.048	D
Polyphen		0.24	B
Vest4		0.13
MutPred		0.11		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.56
MPC		0.087
ClinPred		0.17	T
GERP RS		3.6
Varity_R		0.077
gMVP		0.031
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.024
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1159736769; hg19: chr13-96239795;